Table 2.
Clinical studies regarding the effects of nutraceuticals on the immune system
| Reference | Study population | Nutraceutical | Intervention details/status (duration and dose) | Key findings |
|---|---|---|---|---|
| Qi et al., 2016 | 684 healthy children (5 mon~12 yr) | Vitamin A | Vitamin A deficiency | ·Higher risk of acute respiratory tract infection and diarrhea |
| Sommer et al., 1986 | 5,939 preschool children | Vitamin A | Over 1 yr, 200,000 IU | ·Reduced mortality |
| Imdad et al., 2011 1) | Neonates, infants (1~6 mon) and children (6~59 mon) | Vitamin A | − | ·Reduced all-cause and diarrhea-specific mortality in children (6~59 mon) |
| Aibana et al., 2017 | 889 household contacts of pulmonary tuberculosis | Vitamin A | Vitamin A deficiency | ·Higher risk of occurrence of tuberculosis in a dose-dependent manner |
| Bozonet et al., 2015 | 14 young men (18~30 yr) with suboptimal plasma vitamin C status (<50 μmol/L) | Vitamin C | Two SunGold vitamin C rich kiwi fruit/d, 4 wk | ·Increased neutrophil chemotaxis |
| Hemilä et al., 2013 1) | 11,306 participants | Vitamin C | − | ·Reduction of duration and severity of colds |
| Moreira et al., 2007 1) | 1,603 athletes | Vitamin C | − | ·Reduction of the immunodepression induced by intense exercise and prevention upper respiratory tract infections |
| Petersen et al., 2001 | 20 male recreational runners | Vitamin C+Vitamin E | 21 d, 500 mg+400 mg vitamin E | ·Increased lymphocyte counts following exercise |
| Nieman et al., 2002 | 28 runners | Vitamin C | 8 d, 1,500 mg/d | ·No changes in inflammatory cytokines |
| Wang et al., 2022 1) | 5,711 children with asthma | Vitamin D | − | ·Increased risk of asthma in vitamin D deficient children |
| Ginde et al., 2012 | 18,883 participants (>12 yr) | Vitamin D | − | ·Serum 25(OH)D levels inversely associated with recent upper respiratory tract infections |
| Urashima et al., 2010 | 334 school children | Vitamin D | 4 mon, 1,200 IU/d | ·Reduction of the incidence of Influenza A |
| De La Fuente et al., 2008 | 33 elderly participants | Vitamin E | 3 mon, 200 mg/d | ·Increased lymphocyte proliferation, IL-2 production, neutrophil function, and NK cell activity |
| Meydani et al., 2004 | 617 elderly participants (>65 yr) | Vitamin E | 1 yr, 200 IU/d | ·Protective effect on upper respiratory tract infections, particularly the common cold |
| Cheng et al., 2006 | 51 intensive care patients | Vitamin B6 | 14 d, 50~100 mg/d | ·Increased total lymphocyte count and T-helper and T-suppressor cell levels |
| Huang et al., 2010 | 35 patients with rheumatoid arthritis | Vitamin B6 | 12 wk, 100 mg/d | ·Decreased plasma IL-6 and TNF-α levels significantly |
| Boran et al., 2021 | 611 healthy infants | Vitamin B12 | Vitamin B12 deficiency | ·Reduced percentage of Treg cells ·Increased proinflammatory cytokines levels |
| Tamura et al., 1999 | 19 patients | Vitamin B12 | Vitamin B12 deficiency | ·Decreased number of lymphocytes and CD8+ cells ·Higher CD4+/CD8+ ratio ·Suppressed NK cell activity |
| Kavitha et al., 2022 | 55 HIV positive patients | Vitamin B12 | Vitamin B12 deficiency | ·Reduced NK cell activity ·Increased CD8+ cells |
| Wood et al., 2000 | 45 elderly participants (57~84 yr) | Selenium | 6 mon, 400 μg/d | ·Increased number of T cells ·Improvement in NK cell cytotoxicity |
| Walston et al., 2006 | 619 elderly women | Selenium | Selenium deficiency | ·Increased IL-6 levels ·Increased risk of mortality |
| Baum et al., 1997 | 125 HIV positive patients | Selenium | Selenium deficiency | ·Increased risk of mortality |
| Cirelli et al., 1991 | 12 HIV positive patients | Selenium+Vitamin E | 2 mon, 80 μg/d+25 mg/d vitamin E | ·Symptomatic improvement |
| Bub et al., 2003 | 27 healthy men | Polyphenols (cyanidin glycosides and EGCG) | 2 polyphenol-rich juices, 2 wk, 330 mL/d | ·Increased lymphocyte proliferative responsiveness, IL-2 levels and NK lytic activity |
| Khojah et al., 2018 | 100 patients with rheumatoid arthritis | Resveratrol | 3 mon, 1 g/d | ·Reduced clinical markers and the disease activity score assessment ·Decreased levels of serum levels biochemical markers (i.e., IL-6 and TNF-α) |
| Kim et al., 2020 | 10 patients with inflammatory bowel disease | Polyphenols (gallotannins and gallic acid) | Mango (Mangifera indica L.) pulp, 8 wk, 200~400 g/d | ·Increased the abundance of Lactobacillus spp., Lactobacillus plantarum, Lactobacillus reuteri, and Lactobacillus lactis in the intestinal microbiome ·Improved symptoms of inflammatory bowel disease ·Decreased plasma levels of IL-8 |
| Zhang et al., 2008 | 40 male football players | Phytocompounds from Ganoderma lucidum | Extract isolated from the fruiting body of G. lucidum, 6 wk, 2.5~5.0 g/d | ·Reduction of the CD4+/CD8+ ratio |
| Dai et al., 2015 | 52 healthy participants (21~41 yr) | Phytocompounds from Lentinula edodes (Shiitake) | 4 wk, 5~10 g/d | ·Increased proliferation of γδ T cells and NK cells ·Increased levels of sIgA, IL-4, IL-10, TNF-α, and IL-1α ·Reduced ratio MIP-1α/CCL3 |
| Ahn et al., 2004 | 100 gynecological cancer patients (26~79 yr) | Phytocompounds from Agaricus blazei Murill Kyowa | 6 wk, three packs/d Every 3 wk | ·Increased NK cell activity |
| Bobovčák et al., 2010 | 20 elite athletes | β-Glucan (from Pleurotus ostreatus) | 2 mon, 50 mg/d | ·No reduction of NK cell activity after intensive exercise |
| Bergendiova et al., 2011 | 50 athletes | β-Glucan (from P. ostreatus) | 3 mon, 200 mg/d | ·Reduced incidence of upper respiratory tract infection symptoms ·Increased number of circulating NK cells |
| Jesenak et al., 2013 | 175 children (3~7 yr) | β-Glucan (from P. ostreatus) | 6 mon, 10 mg/kg/d | ·Decreased frequency of respiratory infections, influenza and flu-like illnesses |
| David and Cunningham, 2019 1) | Healthy participants | Phytocompounds from Echinacea purpurea | − | ·Reduced risk of recurrent respiratory infections and related complications |
| Shah et al., 2007 1) | Healthy or with cold participants | Phytocompounds from E. purpurea | − | ·Decreased incidence and duration of the common cold |
| Charan et al., 2016 1) | 377 patients with Dengue fever | Phytocompounds from papaya (Carica papaya) | − | ·Decrease in hospitalization days and increased platelet count |
| Ried, 2016 1) | 970 participants | Phytocompounds from garlic (Allium sativum L.) | − | ·Increased macrophage activity, NK cells, and production of T-and B-cells |
| Ishikawa et al., 2006 | Advanced colon, liver, or pancreatic cancer patients (>65 yr) | Phytocompounds from garlic (A. sativum L.) | Aged garlic extract, 24 wk, 500 mg/d | ·Increased NK cells number and activity |
| Xu et al., 2018 | 51 adults with obesity (25~65 yr) | Phytocompounds from garlic (A. sativum L.) | Aged garlic extract, 6 wk, 3, 6 g/d | ·Prevention of the increase of serum TNF-α and IL-6 concentrations ·Reduced blood LDL concentration |
| Scaglione et al., 1990 | 20 healthy adults | Phytocompounds from Panax ginseng | 8 wk, 200 mg/d | ·Increased phagocytic activity and chemotaxis of PBMCs |
| Scaglione et al., 1996 | 227 participants | Phytocompounds from P. ginseng | Standardized ginseng extract, 12 wk, 100 mg/d | ·Reduced prevalence of colds and the flu |
| Hou et al., 1981 | 14 healthy participants | Phytocompounds from Astragalus membranaceus | 2 mon, 8 g/d | ·Increased interferon-producing capacity of blood cells |
| Kormosh et al., 2006 | 28 ovarian cancer patients in chemotherapy | Phytocompounds from Schisandra chinensis, Leuzea carthamoides, Rhodiola rosea, Eleutherococcus senticosus | Dried ethanol/aqueous extracts, 4 wk, 270 mg/d | ·Boosted suppressed immunity ·Increased numbers of the T cell subclasses and mean amounts of IgG and IgM |
| Lebedev et al, 1970 | 346 school children | Phytocompounds from S. chinensis | S. chinensis seed tincture | ·Reduced rate, duration and clinical manifestations of influenza |
| Xu et al., 2013 | 15 male participants (HDBR experiment) | Phytocompounds from R. rosea | 45 d, 0.5~1.0 g/d | ·Decreased IFN-γ level ·Slowed upregulation of IL-1 family cytokines |
| Mikolai et al., 2009 | 5 participants | Phytocompounds from Withania somnifera | Root extract, 96 h, 12 mL/d | ·Activation of NK cells ·Increased CD4+ T cells |
| Gill et al., 2001 | 27 healthy elderly participants (63~84 yr) | Probiotic (Bifidobacterium lactis HN019) | 3 wk, 5×1010 CFU/d or 5×109 CFU/d | ·Increased helper and activated T cells and NK cells ·Elevated phagocytic capacity of mononuclear and PMN phagocytes and the tumoricidal activity of NK cells |
| Namba et al., 2010 | 27 elderly participants | Probiotic (Bifidobacterium longum BB536) | 5 wk, 1×1011 CFU/d | ·Lower number of participants who contracted influenza ·Increased NK cell activity and neutrophils bactericidal activity |
1)Meta-analysis.
25(OH)D, 25(OH) vitamin D; IL, interleukin; NK, natural killer; TNF-α, tumor necrosis factor-α; HIV, human immunodeficiency virus; CD, cluster of differentiation; ECGC, epigallocatechin gallate; sIgA, secretory immunoglobulin A; MIP-1α/CCL3, macrophage inflammatory protein-1α/chemokine C-C ligand 3; LDL, low-density lipoprotein; PBMC, peripheral blood mononuclear cell; IgG, immunoglobulin G; IgM, immunoglobulin M; HDBR, head-down bed rest; IFN-γ, interferon-γ; CFU, colony-forming unit; PMN, polymorphonuclear leukocyte.